Gene expression is the process by which functional biochemical molecules are produced from information within the gene. RNA splicing is a required step for gene expression in higher eukaryotes, where genes are refined by removing non-coding sequences to leave mature RNA that contains only coding sequences.Splicing is carried out by a macromolecular machine called the spliceosome. The spliceosome is a large complex made up of hundreds of proteins and small RNA molecules. Snu114 is an essential protein in the spliceosome and binding a specific small molecule, fusidic acid, to Snu114 will inhibit the function of the protein and subsequently arrest splicing activity.The inhibition of spliceosome activity is part of continuing work to understand the spliceosome. Splicing is a crucial process in gene expression and a significant number of genetic diseases are cause by mutations that affect splicing.Fusidic acid is an antibiotic steroid and a known inhibitor of Snu114 and existing work has established a structure-activity relationship. It is expected that new synthetic strategies for forming derivatives of fusidic acid and observing how those derivatives bind to Snu114 will give a better insight into how they interact and will lead into ways to develop better splicing inhibitors.
Date of Award | 31 Dec 2014 |
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Original language | English |
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Awarding Institution | - The University of Manchester
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- 3-acetoxy fusidic acid
- snu114
- fusidic acid
- spliceosome
Towards New Synthetic Strategies for Derivatisation of Fusidic Acid: Developing Spliceosome Inhibitors
Bowen, A. (Author). 31 Dec 2014
Student thesis: Master of Philosophy